Studie GS-0201 samostatně a v kombinaci u účastníků s pokročilými solidními nádory

Inclusion Criteria:

• Able to understand and give written informed consent.

• Assigned female or male at birth, 18 years of age or older, and meet the age of majority/adulthood per local regulations.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.

• Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria by investigator assessment.

• Organ function requirements:

  • Adequate hematologic function
  • Adequate hepatic function
  • Creatinine clearance
  • Coagulation

• Tissue requirement:

  • Parts A, B, C, and D:

    • Pre-treatment tumor tissue is required.

  • Parts A and C backfill biopsy cohorts:

    • Individuals must agree to fresh pre- and on-treatment biopsies.

• Individuals assigned male at birth and individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception

• Willing and able to comply with the requirements and restrictions in this protocol

• Part A (GS-0201 Monotherapy Dose Escalation) Inclusion Criteria:

  • Histologically/cytologically confirmed progressive/advanced solid tumors with selected molecular lesions.
  • Individuals must have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy

• Part B (Dose Expansion) Inclusion Criteria:

  • Disease documented as:

  • Cohort B1:

    • Histologically or cytologically confirmed progressive/advanced selected solid tumor diagnoses harboring defined molecular lesions
    • Participants may potentially be required to forgo treatment with approved agent(s) to be able to participate in the study

  • Cohort B2:

    • Histologically or cytologically confirmed progressive/advanced solid tumor diagnoses harboring defined molecular lesions not included in Cohort B1

• Part C (Dose Escalation) Inclusion Criteria:

  • Histologically or cytologically confirmed unresectable locally advanced/metastatic selected solid tumors

• Part D (Dose Expansion) Inclusion Criteria:

  • Disease documented as:

  • Cohort D1:

    • Histologically or cytologically confirmed unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC)

  • Cohort D2:

    • Recurrent/persistent endometrial cancer

Exclusion Criteria:

• Pregnant or lactating females

• Known hypersensitivity to any of the study drugs, its metabolites, or formulation excipients

• Requirement for ongoing therapy with or use of any prohibited medications described in the protocol

• Individuals with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with findings suggestive of MDS/AML

• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of GS-0201

• The therapies listed below within the specified timeframe:

  • Major surgery (excluding minor procedures, eg, placement of vascular access, gastrointestinal/biliary stent, biopsy) < 4 weeks prior to planned Cycle 1 Day 1
  • Immunotherapy or biologic therapy < 21 days prior to planned Cycle 1 Day 1
  • Chemotherapy < 14 days prior to planned Cycle 1 Day 1, or < 42 days for mitomycin or nitrosoureas
  • Targeted small molecule therapy < 14 days prior to planned Cycle 1 Day 1
  • Receipt of experimental therapy within 21 days or 5 experimental treatment half-lives (whichever is longer) prior to planned Cycle 1 Day 1
  • Hormonal or other adjunctive therapy for cancers other than the cancer under evaluation in this study that started < 14 days prior to planned Cycle 1 Day 1 are not permitted. Hormonal therapy, bisphosphonates, somatostatin analogues, and leuprolide are permitted if started ≥ 14 days prior to planned Cycle 1 Day 1
  • Radiotherapy within 2 weeks prior to planned Cycle 1 Day 1 and the radiation is not administered to a target lesion
  • Any prior allogeneic tissue/solid organ transplantation, including allogeneic hematopoietic stem cell transplantation. Individuals with a history of autologous hematopoietic stem cell transplantation are also excluded

• Have not recovered (ie, Grade 1 or lower) from AEs due to a previously administered agent

• Prior treatment with approved or experimental prohibited agents as detailed in the protocol.

• Diagnosis of immunodeficiency, either primary or acquired, or requires systemic corticosteroids (> 10 mg of prednisone daily, or equivalent). However, replacement doses, topical, ophthalmologic, and inhalational steroids are permitted

• Have an active second malignancy

• Have known active central nervous system (CNS) metastases

• Individuals with carcinomatous meningitis or primary CNS tumors are excluded regardless of clinical stability

• Meet any of the following criteria for cardiac disease:

  • Myocardial infarction or unstable angina pectoris within 6 months of enrollment
  • History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication)
  • QT interval > 470 msec
  • New York Heart Association Class III or greater congestive heart failure or known left ventricular ejection fraction less than 40%

• Meet any of the following infectious criteria:

  • Have active serious infection requiring antimicrobials
  • Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV. In individuals with a history of HBV or HCV, individuals with detectable viral loads will be excluded
  • Individuals who test positive for hepatitis B surface antigen. Individuals who test positive for hepatitis B core antibody are eligible with a negative HBV DNA by quantitative Polymerase chain reaction (PCR)
  • Individuals who test positive for HCV antibody. Individuals who test positive for HCV antibody are eligible with a negative HCV RNA by quantitative PCR
  • Individuals who test positive for HIV antibody

• History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or radiation pneumonitis requiring steroids

• Symptomatic ascites or pleural effusion

• Have other concurrent medical or psychiatric conditions that, in the investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations

• Any medical condition that, in the investigator's or sponsor's opinion, poses an undue risk to the individuals participation in the study

• Use of any live vaccines against infectious diseases within 4 weeks (28 days) of initiation of study drug(s) (inactivated, viral vector vaccines, and messenger RNA (mRNA) vaccines are allowed; seasonal vaccines should be up to date prior to planned Cycle 1 Day 1)

• Parts C (Dose Escalation) and D (Dose Expansion): Combination Cohorts:

  • Individuals with active chronic inflammatory bowel disease (ulcerative colitis, Crohn disease) and individuals with a history of bowel obstruction or gastrointestinal perforation within 6 months prior to planned Cycle 1 Day 1
  • Individuals who previously received topoisomerase 1 inhibitors or antibody-drug conjugates containing a topoisomerase 1 inhibitor
  • Known severe intolerance or life-threatening hypersensitivity reactions to humanized monoclonal antibodies or intravenous (IV) immunoglobulin preparations; any history of anaphylaxis; history of human anti-human antibody response

Note: Other protocol defined Inclusion/Exclusion criteria may apply.